ArticlePLoS genetics2014
Serine- and threonine/valine-dependent activation of PDK and Tor orthologs converge on Sch9 to promote aging.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 88 citations in OpenAlex.
- Yeast Chronological Lifespan Model as a Tool for Screening Aging Interventions.International journal of molecular sciences · 2026Review
- Asparagine prevents intestinal stem cell aging via the autophagy-lysosomal pathway.Aging cell · 2025Article
- Serine metabolism in aging and age-related diseases.GeroScience · 2025Review
- Exploring juventology: unlocking the secrets of youthspan and longevity programs.Frontiers in aging · 2024Review
- The Biomarkers in Extreme Longevity: Insights Gained from Metabolomics and Proteomics.International journal of medical sciences · 2024Review
- Branched-chain amino acid synthesis is coupled to TOR activation early in the cell cycle in yeast.EMBO reports · 2023Article
- The Yeast Protein Kinase Sch9 Functions as a Central Nutrient-Responsive Hub That Calibrates Metabolic and Stress-Related Responses.Journal of fungi (Basel, Switzerland) · 2023Review
- Review
- The remoulding of dietary effects on the fecundity / longevity trade-off in a social insect.BMC genomics · 2023Article
- Anti-Aging and Neuroprotective Properties ofNutrients · 2022Article
- Review
- Review
- Histidine kinase two-component response regulators Ssk1, Skn7 and Rim15 differentially control growth, developmental and volatile organic compounds emissions as stress responses in Trichoderma atroviride.Current research in microbial sciences · 2022Article
- Metabolomic Profiles of Mouse Tissues Reveal an Interplay between Aging and Energy Metabolism.Metabolites · 2021Article
- Review
- Amino Acids Whose Intracellular Levels Change Most During Aging Alter Chronological Life Span of Fission Yeast.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Article
- The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging.Frontiers in aging · 2021Review
- Statistical mediation of the relationships between chronological age and lipoproteins by nonessential amino acids in healthy men.Computational and structural biotechnology journal · 2021Article
- Ribosomal Protein uL11 as a Regulator of Metabolic Circuits Related to Aging and Cell Cycle.Cells · 2020Article
- Cell organelles and yeast longevity: an intertwined regulation.Current genetics · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Dietary restriction extends longevity in organisms ranging from bacteria to mice and protects primates from a variety of diseases, but the contribution of each dietary component to aging is poorly understood. Here we demonstrate that glucose and specific amino acids promote stress sensitization and aging through the differential activation of the Ras/cAMP/PKA, PKH1/2 and Tor/S6K pathways. Whereas glucose sensitized cells through a Ras-dependent mechanism, threonine and valine promoted cellular sensitization and aging primarily by activating the Tor/S6K pathway and serine promoted sensitization via PDK1 orthologs Pkh1/2. Serine, threonine and valine activated a signaling network in which Sch9 integrates TORC1 and Pkh signaling via phosphorylation of threonines 570 and 737 and promoted intracellular relocalization and transcriptional inhibition of the stress resistance protein kinase Rim15. Because of the conserved pro-aging role of nutrient and growth signaling pathways in higher eukaryotes, these results raise the possibility that similar mechanisms contribute to aging in mammals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.